Miguel Estévez

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Migraine is an episodic pain disorder whose pathophysiology is related to deficiency of serotonin signaling and abnormal function of the P/Q-type calcium channel, CACNA1A. Because the relationship of the CACNA1A channel to serotonin signaling is unknown and potentially of therapeutic interest we have used genetic analysis of the Caenorhabditis elegans(More)
Selenium is an essential micronutrient that functions as an antioxidant. Yet, at higher concentrations, selenium is pro-oxidant and toxic. In extreme cases, exposures to excess selenium can lead to death or selenosis, a syndrome characterized by teeth, hair and nail loss, and nervous system alterations. Recent interest in selenium as an anti- tumorigenic(More)
Selenium is an essential micronutrient required for cellular antioxidant systems, yet at higher doses it induces oxidative stress. Additionally, in vertebrates environmental exposures to toxic levels of selenium can cause paralysis and death. Here we show that selenium-induced oxidative stress leads to decreased cholinergic signaling and degeneration of(More)
Proper calcium channel and insulin signaling are essential for normal brain development. Leaner mice with a mutation in the P/Q-type voltage-gated calcium channel, Cacna1a, develop cerebellar atrophy and mutations in the homologous human gene are associated with increased migraine and seizure tendency. Similarly, abnormalities in insulin signaling are(More)
IL-15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL-15 antagonist peptide corresponding to sequence 36-45 of IL-15 (KVTAMKCFLL) named P8, which specifically binds(More)
The field of migraine genetics has seen an explosion of information over the last year. In a recent breakthrough, missense mutations in a chromosome 1q23 gene, ATP1A2, encoding a Na+, K+-ATPase, have been identified in four distinct pedigrees with a rare form of familial hemiplegic migraine (FHM). ATP1A2 is expressed in the brain, like the voltage gated(More)
The cAMP-response element binding protein (CREB)-mediated cell signaling pathway is conserved through evolution and participates in a broad range of complex behaviors of divergent species including man. This study describes the integration of genetic, pharmacologic, and anatomic methods to elucidate a serotonergic signaling pathway by which the CREB homolog(More)
Migraine is a chronic episodic disorder that has been linked to abnormalities in serotonin signaling and abnormal function of a presynaptic voltage-gated calcium channel, CACNA1A. Although the importance of serotonin to migraine tendency suggests a link between serotonergic signaling and CACNA1A function, the nature of this connection remains unclear in(More)
Exposures to high levels of environmental selenium have been associated with motor neuron disease in both animals and humans and high levels of selenite have been identified in the cerebrospinal fluid of patients with amyotrophic lateral sclerosis (ALS). We have shown previously that exposures to high levels of sodium selenite in the environment of(More)